Just imagine if the question in the title of this post was, “Why would anyone want access to prescription medications for diabetes?” (or heart disease? or lung disease? or arthritis? or, for that matter, cancer?)
Why would anyone even ask that question?
If there is one thing we know for sure about obesity, it is that it behaves just like every other chronic disease.
Once you have it (no matter how or why you got it) – it pretty much becomes a life-long problem. Our bodies are so efficient in defending our body fat, that no matter what diet or exercise program you go on, ultimately, the body wins out and puts the weight back on.
In those few instances where people claim to have “conquered” obesity, you can virtually bet on it, that they are still dealing with keeping the lost weight off every single day of their life – they are not cured, they are just treated! Their risk of putting the weight back on (recidivism) is virtually 100% – it’s usually just a matter of time.
Funnily enough, this is no different from people trying to control any other chronic disease with diet and exercise alone.
Take for e.g. diabetes. It is not that diet and exercise don’t work for diabetes, but the idea that most people can somehow control their diabetes with diet and exercise alone is simply not true. No matter what diet they go on or what exercise program they follow, sooner or later, their blood sugar levels go back up and the problems come back.
You could pretty much say the same for high blood pressure or cholesterol, or pretty much any other chronic health problem (that, in fact, is the very definition of “chronic”).
So why medications for obesity?
Because, like every other chronic disease, medications can help patients achieve long-term treatment goals (of course only as long as they stay on treatment).
Simply put, if the reason people virtually always regain their lost weight (no matter how hard they try to lose it) is simply because of their body’s ability to resist weight loss and promote weight regain, then medications that interfere with the body’s ability to resist weight loss and promote weight regain, will surely make it far more likely for them to not only lose the weight but also keep it off.
Now that we increasingly understand many of the body’s mechanisms to defend against weight loss and promote weight regain (and the body has a whole bag of tricks that you are up against), then pharmacologically blocking these mechanisms makes this a manageable (fair?) fight.
This is by no means easy. Interfering with human physiology always comes at a cost – which is why we need medications that are robustly tested for safety and efficacy (which is why we are here talking about prescription medications and not the nonsense you can buy over the counter in your local drug store or health supplement outlet).
There is of course no guarantee that any one medication will work for or be tolerated by everyone – again, no different from the medications for other chronic diseases (which is why we have so many of them for the same indication).
So who has access to prescription anti-obesity medications in Canada?
Short answer – almost no one.
Thus, in the 2017 Report Card on Access To Obesity Treatment For Adults, released last week at the 5th Canadian Obesity Summit, the less than 20% of Canadians living with obesity (and that is a very generous estimate) have access to the two prescriptions medications approved by Health Canada for long-term treatment of obesity.
Thus, as far a coverage for obesity medications in Canada is concerned,
Neither anti-obesity medication (Xenical® or saxenda®) are listed as a benefit on any provincial/territorial formulary and, therefore, they are not covered under any provincial public drug benefit (or pharmacare) programs.
There may be special-access programs in some provinces that adjudicate coverage for non-formulary medications based on individual case review; however, coverage for anti-obesity medications through these programs are not guaranteed and are, in fact, rare.
Anti-obesity medications are not covered in any federal public drug benefit programs.
Again one must ask, what will it take for governments, employers, and payers to stop discriminating against Canadians living with obesity in our healthcare system?
Disclaimer: I have received honoraria for speaking and consulting for companies that make anti-obesity medications
Every single guideline on obesity management emphasises the importance of interdisciplinary obesity management by a team that not only consists of a physician and a dietitian but also includes psychologists, exercise specialists, social workers, and other health professionals as deemed necessary.
As is evident from the evident from the 2017 Report Card on Access To Obesity Treatment For Adults, released last week at the 5th Canadian Obesity Summit, the overwhelming majority of Canadians living with obesity have no access to anything that even comes close.
Thus, the report finds that
Among the health services provided at the primary care level for obesity management, dietitian services are most commonly available.
Access to exercise professionals, such as exercise physiologists and kinesiologists, at the primary care level is limited throughout Canada.
Access to mental health support and cognitive behavioural therapy for obesity management at the primary care level is also limited throughout Canada. bariatric surgery programs often have a psychologist or a social worker that offers mental health support and cognitive behavioural therapy to patients on the bariatric surgery route, but the availability of these supports outside of these programs is scarce.
Centres where bariatric surgery is conducted also have inter- disciplinary teams that work within the bariatric surgical programs and provide support for patients on the surgical route.
Alberta and ontario have provincial programs with dedicated bariatric specialty clinics that offer physician-supervised medical programs with interdisciplinary teams for obesity management.
Interdisciplinary teams for obesity management outside of the bariatric surgical programs are available in one out of five regional health authorities (RHa) in british Columbia, one out of 18 RHas in Québec, one out of two RHas in new brunswick and one out of four RHas in newfoundland and labrador.
Among the territories, only yukon has a program with an interdisciplinary team focusing on obesity management in adults.
I hardly need to remind readers, that this is in stark contrast to the resources and teams available to patients with diabetes, heart disease, lung disease, or any other common chronic disease, that are regularly available in virtually every health jurisdiction across the country (not to say that they are perfect or sufficient – but at least there is some level of service available).
I understand that our current obesity treatments are extremely limited (at least when effectiveness is measured in terms of weight loss). But even if access to these resources could simply help stabilise and prevent further weight gain (progression) and perhaps improve overall health and well-being, surely Canadians living with obesity should deserve no less that people living with any other chronic disease.
There is simply no excuse for treating Canadians living with obesity as second-class citizens in our publicly funded healthcare system.
Since the introduction of SGLT-2 inhibitors (“gliflozins” or “glucoretics), as an insulin-independent treatment for type 2 diabetes, that works by blocking glucose reabsorbtion in the kidney resulting in loss of glucose (and calories) through the kidney, much has been written about the (albeit modest) weight loss associated with this treatment.
Several studies have documented that the weight loss leads to a change in body composition with an often significant reduction in fat mass.
Now, Giuseppe Daniele and colleagues, in a paper published in Diabetes Care, show that treatment with these compounds may enhance fat oxidation and increase ketone production in patients with type 2 diabetes.
The researchers randomized 18 individuals with type 2 diabetes to dapagliflozin or placebo for two weeks.
As expected, dapagliflozin reduced fasting plasma glucose significantly (from 167 to 128 mg/dL).
It also increased insulin-stimulated glucose disposal (measured by insulin clamp) by 36%, indicating a significant increase in insulin sensitivity.
Compared to baseline, glucose oxidation decreased by about 20%, whereas nonoxidative glucose disposal (glycogen synthesis) increased by almost 50%.
Moreover, dapagliflozin increased lipid oxidation resulting in a four-fold increase in plasma ketone concentration and and a 30% increase in fasting plasma glucagon.
Thus, the authors note that treatment with dapagliflozine improved insulin sensitivity and caused a shift from glucose to lipid oxidation, which, together with an increase in glucagon-to-insulin ratio, provide the metabolic basis for increased ketone production.
While this may explain the recent observation of a greater (albeit still rather rare) incidence of ketoacidosis with the use of these compounds, these findings may also explain part of the change in body composition previously noted with SGLT-2 treatment.
While this still does not make SGLT-2 inhibitors “weight-loss drugs”, there appears to be more to the fat loss seen with these compounds than just the urinary excretion of glucose.
The biguanide metformin is widely used for the treatment of type 2 diabetes. Metformin has also been shown to slow the progression from pre to full-blown type 2 diabetes. Moreover, metformin can reduce weight gain associated with psychotropic medications and polycystic ovary syndrome.
Now, a randomised controlled trial by M P van der Aa and colleagues from the Netherlands, published in Nutrition & Diabetes suggests that long-term treatment with metformin may stabilize body weight and improve body composition in adolescents with obesity and insulin resistance.
The randomised placebo-controlled double-blinded trial included 62 adolescents with obesity aged 10–16 years old with insulin resistance, who received 2000 mg of metformin or placebo daily and physical training twice weekly over 18 months.
Of the 42 participants (mean age 13, mean BMI 30), BMI was stabilised in the metformin group (+0.2 BMI unit), whereas the control group continued to gain weight (+1.2 BMI units).
While there was no significant difference in HOMA-IR, mean fat percentage reduced by 3% compared to no change in the control group.
Thus, the researcher conclude that long-term treatment with metformin in adolescents with obesity and insulin resistance can result in stabilization of BMI and improved body composition compared with placebo.
Given the rather limited effective options for addressing childhood obesity, this rather safe, simple, and inexpensive treatment may at least provide some relief for adolescents struggling with excess weight gain.
Regular readers may recall previous posts on the novel anti-obesity compound belanorib, a MetAP2 inhibitor that showed remarkable weight loss efficacy both in patients with Prader-Willi Syndrome as well as hypothalamic obesity.
Unfortunately, as noted before, several cases of venous thromoboembolisms led to a halt of ongoing trials during which the company (Zafgen) sought to better understand the possible mechanism for this serious adverse effect and explore the possibility of implementing a risk mitigation strategy.
As announced by the company in a press release earlier this week,
“Following its discussions with the FDA and review of other considerations, Zafgen has determined that the obstacles, costs and development timelines to obtain marketing approval for beloranib are too great to justify additional investment in the program, particularly given the promising emerging profile of ZGN-1061. The Company is therefore suspending further development of beloranib in order to focus its resources on ZGN-1061.”
The press release also describes the new compound ZGN-1061 as a,
“…fumagillin-class, injectable small molecule second generation MetAP2 inhibitor that was discovered by Zafgen’s researchers and has been shown to have an improved profile relative to previous inhibitors in the class. Like other MetAP2 inhibitors that have shown promise in the treatment of metabolic diseases including severe and complicated obesity, ZGN-1061 modulates the activity of key cellular processes that control the body’s ability to make and store fat, and utilize fat and glucose as an energy source. ZGN-1061 is also anticipated to help reduce hunger and restore balance to fat metabolism, enabling calories to once again be used as a productive energy source, leading to weight loss and improved metabolic control. ZGN-1061 has an emerging safety profile and dosage form that are believed to be appropriate for the treatment of prevalent forms of severe and complicated obesity, and is currently in Phase 1 clinical development. Zafgen holds exclusive worldwide rights for the development and commercialization of ZGN-1061.”
According to the press release,
“The compound has similar efficacy, potency, and range of activity in animal models of obesity as beloranib, but displays highly differentiated properties and a reduced potential to impact thrombosis, supporting the value of the compound as a more highly optimized MetAP2 inhibitor.”
Screening of patients for a Phase 1 clinical trial evaluating ZGN-1061 for safety, tolerability, and weight loss efficacy over four weeks of treatment is currently underway.
Disclaimer: I have served as a consultant to Zafgen.